Long Non-Coding RNA 122 (Lnc122) for Treatment Cancer

Abstract

Provided are methods and compositions for reducing proliferation of a target cell (e.g., target cancer cell), e.g., for treating an individual who has cancer. The subjects include the use of an agent that increases activity of long non-coding RNA 122 (lnc122) in the targeted cell(s). As such, a subject method can include a step of administering to the individual a subject composition, which includes an agent that increases activity of lnc122. In some cases, a subject agent is a genome targeting fusion protein (e.g., Zinc Finger, TALE, or CRISPR effector protein fused to a transcriptional activator) that causes increased transcription of lnc122 from its endogenous locus. In some cases, a subject agent is lnc122, or a functional equivalent thereof. In some cases, a subject agent is a nucleic acid that encodes lnc122 or a functional equivalent thereof.

1 . A method for treating cancer, comprising:
 administering to an individual who has cancer a composition comprising an agent that increases activity of long non-coding RNA 122(lnc122) in cancer cells of the individual.   
     
     
         2 . The method of  claim 1 , wherein said agent comprises a genome targeting fusion protein that causes increased transcription of lnc122 from its endogenous locus. 
     
     
         3 . The method of  claim 2 , wherein said genome targeting fusion protein is a CRISPRa agent, a Zinc Finger (ZF) or TALE agent. 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein said agent comprises: (i) lnc122, or a functional equivalent thereof; or (ii) a nucleic acid that encodes said lnc122 or encodes said functional equivalent thereof. 
     
     
         6 - 11 . (canceled) 
     
     
         12 . The method of  claim 5 , wherein said nucleic acid is a viral vector, a plasmid DNA, a minicircle DNA, or a doggybone DNA. 
     
     
         13 - 15 . (canceled) 
     
     
         16 . The method of  claim 5 , wherein the agent comprises a nanoparticle that comprises (i) and/or (ii). 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 1 , wherein the cancer is liver cancer, lung cancer, ovarian cancer, prostate cancer, colorectal cancer, renal cancer, bladder cancer, breast cancer, thyroid cancer, pleural cancer, pancreatic cancer, uterine cancer, cervical cancer, testicular cancer, anal cancer, bile duct cancer, gastrointestinal carcinoid tumors, esophageal cancer, gall bladder cancer, appendix cancer, small intestine cancer, gastric cancer, cancer of the central nervous system, skin cancer, head and neck cancer, or blood cancer. 
     
     
         19 . The method of  claim 1 , wherein the cancer is characterized by Myc deregulation. 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the cancer is hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, or hepatoblastoma. 
     
     
         22 - 27 . (canceled) 
     
     
         28 . The method of  claim 1 , wherein said administering comprises systemic administration. 
     
     
         29 - 34 . (canceled) 
     
     
         35 . A method of reducing proliferation of a target cancer cell, the method comprising:
 introducing into a target cancer cell a composition comprising an agent that increases activity of long non-coding RNA 122(lnc122) in the target cancer cell,   wherein said introducing results in reduced proliferation of the target cancer cell.   
     
     
         36 . The method of  claim 35 , wherein the target cancer cell is in vitro. 
     
     
         37 . (canceled) 
     
     
         38 . The method of  claim 35 , wherein said introducing comprises administering said composition to an individual comprising said target cancer cell. 
     
     
         39 . The method of  claim 35 , wherein said agent comprises a genome targeting fusion protein that causes increased transcription of lnc122 from its endogenous locus. 
     
     
         40 . The method of  claim 39 , wherein said genome targeting fusion protein is a CRISPRa agent, a Zinc Finger (ZF), or a TALE agent. 
     
     
         41 . The method of  claim 35 , wherein said agent comprises: (i) lnc122, or a functional equivalent thereof; or (ii) a nucleic acid that encodes said lnc122 or encodes said functional equivalent thereof. 
     
     
         42 . The method of  claim 41 , wherein said functional equivalent thereof comprises a nucleotide sequence having 85% or more sequence identity with the lnc122 sequence set forth as SEQ ID NO: 5 or 6. 
     
     
         43 - 45 . (canceled) 
     
     
         46 . The method of  claim 41 , wherein said nucleic acid is a viral vector, a plasmid DNA, a minicircle DNA, or a doggybone DNA. 
     
     
         47 - 56 . (canceled) 
     
     
         57 . A composition, comprising:
 an agent that increases activity of long non-coding RNA 122(lnc122) in target cells, wherein said composition is formulated for administration into an individual who has cancer.   
     
     
         58 . The composition of  claim 57 , wherein said agent comprises a genome targeting fusion protein that causes increased transcription of lnc122 from its endogenous locus. 
     
     
         59 . (canceled) 
     
     
         60 . The composition of  claim 57 , wherein said agent comprises: (i) lnc122, or a functional equivalent thereof; or (ii) a nucleic acid that encodes said lnc122 or encodes said functional equivalent thereof. 
     
     
         61 - 68 . (canceled) 
     
     
         69 . A recombinant viral vector, comprising:
 a nucleotide sequence encoding lnc122 or an equivalent thereof, wherein said nucleotide sequence is operably linked to a heterologous promoter.   
     
     
         70 - 72 . (canceled) 
     
     
         73 . The recombinant viral vector of  claim 69 , wherein the recombinant viral vector is an AAV vector or a retroviral vector. 
     
     
         74 - 75 . (canceled)